What Causes Strep Throat?

Beta-hemolytic group A streptococcus or Streptococcus pyogenes, a gram-positive human pathogen that habitually colonizes the throat or skin of the host, is a cause of streptococcal pharyngitis – more commonly known as “strep throat”. Infections with this microorganism are underpinned by a panoply of virulence factors that are produced in direct response to environmental signals in the host.

Streptococcus pyogenes – the causative organism

Streptococcus pyogenes is a bacterium that requires complex media with blood products for growth, which is best achieved in an environment of 10% carbon dioxide. On blood agar plates group A streptococci produce pinpoint colonies surrounded by a zone of complete beta-hemolysis.

Its cell wall consists of a peptidoglycan backbone with integral lipoteichoic acid components that aid in structural stability. Akin to endotoxin from gram-negative bacteria, peptidoglycan is capable of activating the alternative complement pathway (which is a major effector of humoral part of our immune system).

Lancefield classification, which was developed by Rebecca Craighill Lancefield in the early years of the 20th century, distinguishes Streptococcus pyogenes from other representatives of the genus by identifying unique extractable carbohydrate antigen of cell wall material. Moreover, beta-hemolytic group A streptococcus have been further subdivided according to the surface expression of M and T antigens.

Such typing and subtyping endeavors have been of great significance in streptococcal epidemiology (similar to phage typing in epidemiology of Staphylococcus aureus). High-resolution genotyping can be used to determine specific relatedness among strains isolated from outbreaks of streptococcal pharyngitis, whereas rapid sequencing of the gene that encodes for M-protein is a fast and definite way of comparing M-typeable and M-non-typeable strains.

Lipoteichoic acid represents an important pro-inflammatory molecule that contributes to adherence of beta-hemolytic group A streptococcus by binding fibronectin OH host cells. Together with various cell surface molecules (including the adhesins), F protein, glyceraldehyde 3-phosphate dehydrogenase and enolase, it is involved in the attachment of the bacteria to the epithelium.

Pathogenic mechanisms of infection

Adherence and subsequent growth of Streptococcus pyogenes on pharyngeal mucosal surfaces are usually sufficient to cause the clinical entity of streptococcal pharyngitis. Adhering to epithelial cells is a prerequisite event in the disease pathogenesis, which is facilitated by fibronectin binding protein or protein F (although M-protein and peptidoglycan may also contribute).

In vitro studies have clearly shown that group-A beta-hemolytic streptococcus can not only adhere to, but invade respiratory epithelial cell lines in tissue culture; in addition, the pathogen has also been found intracellularly in tonsillar tissue from patients with chronic tonsillitis. Still, there are no data suggesting that there is an active invasion of respiratory epithelial cells during acute pharyngitis.

Together with M-protein, think capsules formed of hyaluronic acid found in some strains of Streptococcus pyogenes confer resistance to phagocytosis. The microorganism can also stimulate T cell responses and cytokine induction, resulting in fever and further tissue injury. This can be especially important in the development of complications that can be provoked by certain strains of streptococci.

The immunological response of the host to streptococcal infection is characterized by the production of antibodies against a myriad of streptococcal cellular and extracellular constituents. Host responses against the aforementioned M-protein serotype can protect from reinfection with that specific serotype.

Further Reading

• All Strep Throat Content
• What is Strep Throat?
• How is Strep Throat Diagnosed?
• Strep Throat Treatments

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.